Exam 5 - Fibrates, BAS, Niacin Flashcards
Fibric acid derivatives MOA:
PPARα agonist:
a. Reduces expression of apoC-III
b. Increases lipoprotein lipase activity and lowers VLDL
c. Inhibits triglyceride synthesis
d. Increases hepatic fatty acid oxidation
e. Increases apoA-I and apoA-II and therefore increases HDL
Fibric acid derivatives PK:
a. Food increases BA
b. Prodrug activation via ester hydrolysis
c. Metabolized via glucouronidation
d. Renal elimination
Fibric acid derivatives AE:
a. GI - (all related)
b. Cholelithiasis
c. Rhabdomyolysis and myopathy - both rare
Fibric acid derivatives DDIs (all):
a. anti-diabetes (increases hypoglycemic effects)
b. oral anti coags (increases hypothrombotic effects)
c. ezetimibe (increases r/f cholelithiasis
d. HMG-CoA Reductase Inhibitors (increases risk for myopathy and rhabdomyolysis)
e. BAS (decreases absorption if not spaced)
Clofibrate (Atromid-S) MOA:
PPARα agonist
Clofibrate (Atromid-S) PK special from others fibrates:
Highly bound to albumin
Clofibrate (Atromid-S) contraindications:
Hepatic and renal impairment
Fenofibrate (Tricor, Triglie) MOA:
PPARα agonist
Fenofibrate (Tricor, Triglie) t1/2:
t1/2 = 20 hrs
Fenofibrate (Tricor, Triglie) DDI special from others fibrates:
cyclosporine (increases risk for nephrotoxicity)
Gemfibrozil (Lopid) MOA:
PPARα agonist
Gemfibrozil (Lopid) t/2:
t1/2 = 2 hrs
Gemfibrozil (Lopid) DDIs special from other fibrates:
a. Bexarotene (increases Cp)
b. Repaglinide (increases Cp)
c. Substrates for CYP 2C family metabolism
Niacin (nicotinic acid) MOA:
a. Agonist at niacin GPCR (Gαi) - decreases hormone-sensitive lipase
b. Inhibits lipolysis in adipose tissue to decrease triglycerides
c. Stimulation of lipoprotein lipase –> decreases VLDL secretion and subsequent decrease in LDL
Niacin (nicotinic acid) t1/2:
t1/2 = 1hr
